Cerebral Vessel Wall Diseases

  • Keun-Hwa Jung
Part of the Stroke Revisited book series (STROREV)


The cerebral arterial wall is composed of three layers, the tunica intima, tunica media, and adventitia, which are common structures in human systemic arteries. As the composition and cellular origin of each component differ according to the vessel locations, such as intracranial, extracranial, anterior, and posterior, the response and vulnerability to injury vary for each arterial site. Cerebral vessel wall diseases are characterized by the partial or complete involvement of vascular wall components by an inciting factor. Typical manifestations include transient ischemic attack, cerebral infarction, or intracranial bleeding by luminal narrowing, thrombus formation, or rupture. The main pathophysiological sequence of cerebral vessel wall diseases includes endothelial dysfunction, smooth muscle cell proliferation or degeneration, extracellular matrix degeneration, inflammation, and rheological stress. This chapter deals with three typical cerebral vessel wall diseases including moyamoya disease, arterial dissection, and vasculitis. The cerebral vessel wall diseases may require early differential diagnosis because they are associated with different therapeutic options. However, the early diagnosis may be difficult because these diseases often share clinical manifestations and angiographic features. Recently, the advent of vessel wall imaging techniques and the increasing availability of pathological studies prompt us to better differentiate the diseases and identify the pathomechanism of each disease. This chapter reviews the advances in the histopathological and clinical data of cerebral vessel wall diseases with the aim of unraveling their pathophysiology.


  1. 1.
    Uehara T, Tabuchi M, Mori E, Yamadori A. Evolving atherosclerosis at carotid and intracranial arteries in Japanese patients with ischemic heart disease: a 5-year longitudinal study with MR angiography. Eur J Neurol. 2003;10(5):507–12.PubMedGoogle Scholar
  2. 2.
    Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev. 2009;89(3):957–89.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Walmsley JG. Vascular smooth muscle orientation in curved branches and bifurcations of human cerebral arteries. J Microsc. 1983;131(Pt 3):377–89.PubMedGoogle Scholar
  4. 4.
    Arribas SM, Hinek A, Gonzalez MC. Elastic fibres and vascular structure in hypertension. Pharmacol Ther. 2006;111(3):771–91.PubMedGoogle Scholar
  5. 5.
    Qiao Y, Anwar Z, Intrapiromkul J, Liu L, Zeiler SR, Leigh R, et al. Patterns and implications of intracranial arterial remodeling in stroke patients. Stroke. 2016;47(2):434–40.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Majesky MW. Developmental basis of vascular smooth muscle diversity. Arterioscler Thromb Vasc Biol. 2007;27(6):1248–58.PubMedGoogle Scholar
  7. 7.
    Etchevers HC, Vincent C, Le Douarin NM, Couly GF. The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain. Development (Cambridge, England). 2001;128(7):1059–68.Google Scholar
  8. 8.
    Schievink WI, Raissi SS, Maya MM, Velebir A. Screening for intracranial aneurysms in patients with bicuspid aortic valve. Neurology. 2010;74(18):1430–3.PubMedGoogle Scholar
  9. 9.
    Tadros TM, Klein MD, Shapira OM. Ascending aortic dilatation associated with bicuspid aortic valve: pathophysiology, molecular biology, and clinical implications. Circulation. 2009;119(6):880–90.PubMedGoogle Scholar
  10. 10.
    Dumont AS, Hyndman ME, Dumont RJ, Fedak PM, Kassell NF, Sutherland GR, et al. Improvement of endothelial function in insulin-resistant carotid arteries treated with pravastatin. J Neurosurg. 2001;95(3):466–71.PubMedGoogle Scholar
  11. 11.
    Alexander MR, Owens GK. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu Rev Physiol. 2012;74:13–40.PubMedGoogle Scholar
  12. 12.
    Clarke MC, Littlewood TD, Figg N, Maguire JJ, Davenport AP, Goddard M, et al. Chronic apoptosis of vascular smooth muscle cells accelerates atherosclerosis and promotes calcification and medial degeneration. Circ Res. 2008;102(12):1529–38.PubMedGoogle Scholar
  13. 13.
    Boyle JJ, Weissberg PL, Bennett MR. Human macrophage-induced vascular smooth muscle cell apoptosis requires NO enhancement of Fas/Fas-L interactions. Arterioscler Thromb Vasc Biol. 2002;22(10):1624–30.PubMedGoogle Scholar
  14. 14.
    Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476–85.PubMedGoogle Scholar
  15. 15.
    Guillon B, Peynet J, Bertrand M, Benslamia L, Bousser MG, Tzourio C. Do extracellular-matrix-regulating enzymes play a role in cervical artery dissection? Cerebrovasc Dis (Basel, Switzerland). 2007;23(4):299–303.Google Scholar
  16. 16.
    Nuki Y, Matsumoto MM, Tsang E, Young WL, van Rooijen N, Kurihara C, et al. Roles of macrophages in flow-induced outward vascular remodeling. J Cereb Blood Flow Metab. 2009;29(3):495–503.PubMedGoogle Scholar
  17. 17.
    Berk BC. Atheroprotective signaling mechanisms activated by steady laminar flow in endothelial cells. Circulation. 2008;117(8):1082–9.PubMedGoogle Scholar
  18. 18.
    Sho E, Sho M, Singh TM, Nanjo H, Komatsu M, Xu C, et al. Arterial enlargement in response to high flow requires early expression of matrix metalloproteinases to degrade extracellular matrix. Exp Mol Pathol. 2002;73(2):142–53.PubMedGoogle Scholar
  19. 19.
    Papaioannou TG, Stefanadis C. Vascular wall shear stress: basic principles and methods. Hell J Cardiol. 2005;46(1):9–15.Google Scholar
  20. 20.
    Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington State and California. Neurology. 2005;65(6):956–8.PubMedGoogle Scholar
  21. 21.
    Liu W, Hashikata H, Inoue K, Matsuura N, Mineharu Y, Kobayashi H, et al. A rare Asian founder polymorphism of raptor may explain the high prevalence of Moyamoya disease among east Asians and its low prevalence among Caucasians. Environ Health Prev Med. 2010;15(2):94–104.PubMedGoogle Scholar
  22. 22.
    Hallemeier CL, Rich KM, Grubb RL Jr, Chicoine MR, Moran CJ, Cross DT 3rd, et al. Clinical features and outcome in north American adults with moyamoya phenomenon. Stroke. 2006;37(6):1490–6.PubMedGoogle Scholar
  23. 23.
    Mossa-Basha M, de Havenon A, Becker KJ, Hallam DK, Levitt MR, Cohen WA, et al. Added value of vessel wall magnetic resonance imaging in the differentiation of Moyamoya vasculopathies in a non-Asian cohort. Stroke. 2016;47(7):1782–8.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Kim JM, Jung KH, Sohn CH, Park J, Moon J, Han MH, et al. High-resolution MR technique can distinguish moyamoya disease from atherosclerotic occlusion. Neurology. 2013;80(8):775–6.PubMedGoogle Scholar
  25. 25.
    Ryoo S, Cha J, Kim SJ, Choi JW, Ki CS, Kim KH, et al. High-resolution magnetic resonance wall imaging findings of Moyamoya disease. Stroke. 2014;45(8):2457–60.PubMedGoogle Scholar
  26. 26.
    Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, et al. Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet. 2009;84(5):617–27.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Kamada F, Aoki Y, Narisawa A, Abe Y, Komatsuzaki S, Kikuchi A, et al. A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. J Hum Genet. 2011;56(1):34–40.PubMedGoogle Scholar
  28. 28.
    Bang OY, Fujimura M, Kim SK. The pathophysiology of Moyamoya disease: an update. J Stroke. 2016;18(1):12–20.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Yamada H, Deguchi K, Tanigawara T, Takenaka K, Nishimura Y, Shinoda J, et al. The relationship between moyamoya disease and bacterial infection. Clin Neurol Neurosurg. 1997;99(Suppl 2):S221–4.PubMedGoogle Scholar
  30. 30.
    Lin R, Xie Z, Zhang J, Xu H, Su H, Tan X, et al. Clinical and immunopathological features of Moyamoya disease. PLoS One. 2012;7(4):e36386.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Jeon JS, Ahn JH, Moon YJ, Cho WS, Son YJ, Kim SK, et al. Expression of cellular retinoic acid-binding protein-I (CRABP-I) in the cerebrospinal fluid of adult onset moyamoya disease and its association with clinical presentation and postoperative haemodynamic change. J Neurol Neurosurg Psychiatry. 2014;85(7):726–31.PubMedGoogle Scholar
  32. 32.
    Jung KH, Chu K, Lee ST, Park HK, Kim DH, Kim JH, et al. Circulating endothelial progenitor cells as a pathogenetic marker of moyamoya disease. J Cereb Blood Flow Metab. 2008;28(11):1795–803.PubMedGoogle Scholar
  33. 33.
    Kang HS, Moon YJ, Kim YY, Park WY, Park AK, Wang KC, et al. Smooth-muscle progenitor cells isolated from patients with moyamoya disease: novel experimental cell model. J Neurosurg. 2014;120(2):415–25.PubMedGoogle Scholar
  34. 34.
    Lee WJ, Jung KH, Lee KJ, Kim JM, Lee ST, Chu K, et al. Sonographic findings associated with stenosis progression and vascular complications in moyamoya disease. J Neurosurg. 2016;125(3):689–97.PubMedGoogle Scholar
  35. 35.
    Haneline M, Triano J. Cervical artery dissection. A comparison of highly dynamic mechanisms: manipulation versus motor vehicle collision. J Manip Physiol Ther. 2005;28(1):57–63.Google Scholar
  36. 36.
    Debette S, Leys D. Cervical-artery dissections: predisposing factors, diagnosis, and outcome. Lancet Neurol. 2009;8(7):668–78.PubMedGoogle Scholar
  37. 37.
    Dziewas R, Konrad C, Drager B, Evers S, Besselmann M, Ludemann P, et al. Cervical artery dissection-clinical features, risk factors, therapy and outcome in 126 patients. J Neurol. 2003;250(10):1179–84.PubMedGoogle Scholar
  38. 38.
    Touze E, Gauvrit JY, Moulin T, Meder JF, Bracard S, Mas JL. Risk of stroke and recurrent dissection after a cervical artery dissection: a multicenter study. Neurology. 2003;61(10):1347–51.PubMedGoogle Scholar
  39. 39.
    Kennedy F, Lanfranconi S, Hicks C, Reid J, Gompertz P, Price C, et al. Antiplatelets vs anticoagulation for dissection: CADISS nonrandomized arm and meta-analysis. Neurology. 2012;79(7):686–9.PubMedGoogle Scholar
  40. 40.
    Debette S, Grond-Ginsbach C, Bodenant M, Kloss M, Engelter S, Metso T, et al. Differential features of carotid and vertebral artery dissections: the CADISP study. Neurology. 2011;77(12):1174–81.PubMedGoogle Scholar
  41. 41.
    Morris NA, Merkler AE, Gialdini G, Kamel H. Timing of incident stroke risk after cervical artery dissection presenting without ischemia. Stroke. 2017;48(3):551–5.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Lee WJ, Jung KH, Moon J, Lee ST, Chu K, Lee SK, et al. Prognosis of spontaneous cervical artery dissection and transcranial Doppler findings associated with clinical outcomes. Eur Radiol. 2016;26(5):1284–91.PubMedGoogle Scholar
  43. 43.
    Southerland AM, Meschia JF, Worrall BB. Shared associations of nonatherosclerotic, large-vessel, cerebrovascular arteriopathies: considering intracranial aneurysms, cervical artery dissection, moyamoya disease and fibromuscular dysplasia. Curr Opin Neurol. 2013;26(1):13–28.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Brandt T, Morcher M, Hausser I. Association of cervical artery dissection with connective tissue abnormalities in skin and arteries. Front Neurol Neurosci. 2005;20:16–29.PubMedGoogle Scholar
  45. 45.
    Tzourio C, Cohen A, Lamisse N, Biousse V, Bousser MG. Aortic root dilatation in patients with spontaneous cervical artery dissection. Circulation. 1997;95(10):2351–3.PubMedGoogle Scholar
  46. 46.
    Callaghan FM, Luechinger R, Kurtcuoglu V, Sarikaya H, Poulikakos D, Baumgartner RW. Wall stress of the cervical carotid artery in patients with carotid dissection: a case-control study. Am J Physiol Heart Circ Physiol. 2011;300(4):H1451–8.PubMedGoogle Scholar
  47. 47.
    Salvarani C, Brown RD Jr, Calamia KT, Christianson TJ, Weigand SD, Miller DV, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007;62(5):442–51.PubMedGoogle Scholar
  48. 48.
    Obusez EC, Hui F, Hajj-Ali RA, Cerejo R, Calabrese LH, Hammad T, et al. High-resolution MRI vessel wall imaging: spatial and temporal patterns of reversible cerebral vasoconstriction syndrome and central nervous system vasculitis. AJNR Am J Neuroradiol. 2014;35(8):1527–32.PubMedGoogle Scholar
  49. 49.
    Miller DV, Salvarani C, Hunder GG, Brown RD, Parisi JE, Christianson TJ, et al. Biopsy findings in primary angiitis of the central nervous system. Am J Surg Pathol. 2009;33(1):35–43.PubMedGoogle Scholar
  50. 50.
    Iwase T, Ojika K, Mitake S, Katada E, Katano H, Mase M, et al. Involvement of CD45RO+ T lymphocyte infiltration in a patient with primary angiitis of the central nervous system restricted to small vessels. Eur Neurol. 2001;45(3):184–5.PubMedGoogle Scholar
  51. 51.
    Boulouis G, de Boysson H, Zuber M, Guillevin L, Meary E, Costalat V, et al. Primary Angiitis of the central nervous system: magnetic resonance imaging Spectrum of parenchymal, meningeal, and vascular lesions at baseline. Stroke. 2017;48(5):1248–55.PubMedGoogle Scholar
  52. 52.
    Singhal AB, Topcuoglu MA, Fok JW, Kursun O, Nogueira RG, Frosch MP, et al. Reversible cerebral vasoconstriction syndromes and primary angiitis of the central nervous system: clinical, imaging, and angiographic comparison. Ann Neurol. 2016;79(6):882–94.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Singapore 2020

Authors and Affiliations

  • Keun-Hwa Jung
    • 1
  1. 1.Department of NeurologySeoul National University HospitalSeoulRepublic of Korea

Personalised recommendations